Women of childbearing age may be especially affected by the use and misuse of opioids, however, the reproductive health effects of opioids on infertility treatment is rarely discussed.
The use and misuse of opioids in the US have reached epidemic proportions and women of childbearing age may be especially affected. While many of the consequences have been well-documented – abuse, injury, death from overdose – the impact on fertility and infertility treatment is largely left out of the discussion. That must change.
To define terms, opiate refers to natural substances that come from opium that can be extracted from the opium poppy, containing chemical compounds including morphine and codeine. Opioids are synthetic/semi-synthetic products that work by binding to the same receptors as opiates. Synthetic opioids include fentanyl and methadone; oxycodone and hydrocodone are examples of semi-synthetic opioids.
Opioids and fertility
Greater awareness and education is needed on the use of opioids among women and men considering having children or undergoing infertility treatment for both patients and doctors. Last year, the American Society for Reproductive Medicine (ASRM), the professional society of fertility specialists (reproductive endocrinologists) authored “Opioids and Reproductive Medicine: A Special Views and Reviews Section” in the clinical journal Fertility and Sterility, August 2017 issue. The goal was to address the risks of opioids to those seeking fertility care, especially women of reproductive age, those “most at risk for opioid accidents and addiction.”
“Most reproductive medicine specialists continue to practice as if it is not a phenomenon relevant to their patients,” says former ASRM President Richard J. Paulson, MD, “even as the epidemic has escalated.” He considers the special section “essential reading for all clinicians treating reproductive-age women.”
There are several important reasons to pay special attention to opioid use and fertility:
- In 2015, more than 40% of women between the ages of 15-44 reported they were prescribed at least one opiate prescription.
- There’s a strong overlap among patient demographics for opioid use disorder and fertility treatment. Pre-conception screening revealed women were more likely to have a substance use disorder than other conditions.
- Research shows that long-term use or misuse of opioids affects fertility in both men and women and may also cause sexual dysfunction, loss of libido and depression – all of which may affect the ability to get pregnant and deliver a healthy baby.
Use of Opioids in Fertility Treatment
This class of drugs is traditionally prescribed for pain relief following surgery, an acute injury or for chronic pain. Some women who undergo surgery to correct issues related to infertility or certain procedures may experience major pain for which they are prescribed opioids. Research on opioid prescription patterns following one procedure – egg retrieval for in vitro fertilization (IVF) – offered surprising results.
Researchers analyzed a large data set covering eleven years and found an apparent “disconnect between expected procedural pain and the use of opioids.” Women were more likely to fill an opioid prescription if they had mood disorders, had filled a prescription for an anti-depressant or were smokers. There was also significant variation by geography: 21% of women in the South filled a prescription; only 5% in the Northeast did so. Overall, only 12% of women used opioids after egg retrieval.
The study reviewed medical records for more than 55,000 women who had the egg retrieval procedure (those with a prior diagnosis of opioid or substance use disorder and women who filled more than one opioid prescription in the 12-week period before the procedure were excluded). The researchers concluded that while a small proportion of women undergoing an egg retrieval procedure fill an opioid prescription afterward, those who do “receive a large quantity of opioids.” They suggest that as most women will tolerate the procedure without opioids “this should prompt physicians who routinely prescribe these medications to reevaluate this practice.”
Commenting on this research presented at the 2017 ASRM Scientific Congress, ASRM President Christos Coutifaris MD, Ph.D., concluded
“It is imperative that physicians treating couples with infertility not contribute to the widespread opioid abuse crisis. This kind of research raises our awareness of the potential for abuse and, hopefully, makes us cautious with our prescription patterns.”
Hopefully, the greatly increased attention to the potential dangers of opioids has altered all physician prescribing patterns to find alternatives or sharply limit the time frame for use and amount of drug prescribed.
It is critically important to discuss alternatives to using opioids as “recent data suggest that opioid exposure after other surgeries confers an increased risk for chronic opioid use” and potential for relapse for those with a former opioid use disorder. Alternatives include nonsteroidal anti-inflammatory drugs; acetaminophen (e.g. Tylenol) and other adjunctive medications (not typically used for pain but helpful for management) and regional anesthetic blocks. A variety of strategies to reduce opioid use before and after medical procedures is discussed In Perioperative Pain Management Strategies Among Women Having Reproductive Surgeries, Prahbu et al.
Opioid Substance Use Disorder and Infertility
The stress of receiving a diagnosis of infertility and undergoing treatment can make patients “vulnerable to anxiety and depression, increasing their risk of developing a substance use disorder (SUD)” according to Tricia Wright, MD, MS. Dr. Wright notes pre-conception screening reveals “substance use disorders are more common than many other conditions and disorders in women trying to conceive” in Screening, Brief Intervention, and Referral to Treatment for Opioid and Other Substance Use During Infertility Treatment.
Misuse of opioids includes continuing to use them after the recommended period, taking the drug unrelated to any prescribed reason or using a street version. This can “worsen infertility, complicate pregnancy, increase medical problems, and lead to psychosocial difficulties for the woman and her family.”Given these serious consequences,
Dr. Wright believes that reproductive endocrinologists have an “ethical and medical duty to screen patients” for such disorders, as well as provide initial counseling and referrals to specialized treatment.
As physicians treating women who are planning to become pregnant, she adds her colleagues are “well placed to help their patients avoid the consequences of SUDs in pregnancy, such as pre-term birth, low birth weight, birth defects, developmental delays, miscarriage and neonatal abstinence syndrome.”
At the same time, some opioids – such as methadone – are used to treat addiction. If someone is on this type of drug as part of addiction treatment, they should discuss the impact on fertility with their addiction counselor and other relevant health professionals. Some treatments are less harmful to fertility than others and should be considered.
ASRM acknowledges there is little information on the treatment of opioid use disorder among the infertility population and the best approach may be to learn from the successful treatment of pregnant patients with the condition.
How Do Opioids Affect Fertility?
Research shows that opioid use affects the endocrine system – including the hypothalamic-pituitary axis – which controls the production of sex hormones. Hormonal suppression can lead to inappropriately low levels of gonadotropins (follicle stimulating hormone and luteinizing hormone) and inadequate production of sex hormones, particularly testosterone which plays a role in male and female reproduction.
Opioids affect the female reproductive system including “various parts of the ovary, including ovarian follicles and oocytes (immature egg cells) and may affect the endometrium (tissue lining the uterus) and myometrium (middle layer of the uterine wall) which all have a role in pregnancy. The hormonal suppression may result in menstrual irregularities, potential problems getting pregnant, miscarriages and many pregnancy-related issues including pre-term birth, low birth weight, birth defects and developmental delays.
Using opioids long term can disrupt the signals controlling the production of testosterone resulting in low testosterone production, which in turn can decrease both the quantity and quality of sperm. The actual impact depends on the drug used, the dose and the length of time taken. Low testosterone also affects male libido; one study of men on long-term, high doses of opioids showed 20 percent had evidence of sexual dysfunction. The researchers suggest the same may also be true for women but “evidence is scarce.”
There is no evidence that short-term use of opioids has a negative effect on male fertility. So, if the drug is taken to control pain after surgery or a broken bone, a patient should follow instructions to take only as prescribed.
Men who are taking opioids for weeks or months should talk to their doctor about cutting back. Opioid-induced hypogonadism is often a complication of long-term therapeutic use – for chronic pain or addiction – or illegal use. Experts suggest if this occurs that “nonopioid pain management, opioid rotation, or hormone supplementation” should be tried after “careful consideration of the risks and benefits.”
The Role of Your Doctor
Your fertility specialist should work with you and your partner to understand how a variety of positive and negative lifestyle habits affect your ability to get pregnant and deliver a healthy baby. The use of opioids – whether prescribed for a specific condition or because of a substance use disorder – should be discussed. Good patient-doctor communication should be two way: a 2015 FDA safety report on opioids urges patients to report symptoms such as lack of menstruation, low libido, erectile dysfunction or infertility to their doctors.
Given how often opioids have been prescribed for chronic pain and overlap in the patient demographics for misuse and fertility treatment, there are important ways to improve patient care. Doctors should find alternatives to prescribe for pain relief or addiction treatment, add opioid screening to patient assessment, monitor patients and manage endocrine complications including routine screening for issues and for laboratory abnormalities in sex hormones.
If you need pain relief from surgery, discuss alternatives to opioids. If treatment for opioid use disorder is needed, your physician can offer or arrange counseling – often through your fertility clinic and/or provide a referral to specialized treatment. To address the “unique needs” of a woman planning a pregnancy who also requires treatment for opioid use disorder there are four “overlapping domains of treatment: medication management, medical care, behavioral and mental health care, and psychosocial support” discussed by Hand et al in Treatments for Opioid Use Disorder Among Pregnant and Reproductive-Aged Women.
Undergoing treatment for infertility is challenging and there are many lifestyle habits to follow or change in order to maximize your chances for success. As opioid use may affect getting pregnant and delivering a healthy baby, awareness and education should be part of the partnership between hopeful parents-to-be and their doctors.